Persons with chronic spinal cord injury (SCI) have markedly reduced bone mass and the loss of skeletal architectural integrity, which predisposes them to low-impact fractures. Currently, there is no practical treatment to reverse the severe bone loss in persons with chronic SCI. In the proposed study, a dual pharmacological intervention will be tested to improve bone health. Restoration of bone mass below the level of injury would be expected to reduce the morbidity associated with fractures and permit safer participation in upright activities. Quality of life would be substantially improved because of the ability to engage more securely in activities of daily living and to integrate into the community. Despite the depressed skeletal activity below the level of lesion in persons with chronic SCI, net bone loss occurs because resorption exceeds formation, with a difference between these rates in those with SCI being greater than that observed in the able-bodied population. Thus, it would be anticipated to be of value in persons with chronic SCI to increase bone turnover with the objective to increase bone formation over that of bone resorption. In a preclinical study that administered an anti-sclerostin antibody to rats 12 weeks after complete spinal cord transection bone, mineral density (BMD) was almost fully restored at the distal femoral metaphysis, with improved bone structure, and mechanical strength; in contrast, vehicle-treated animals after complete spinal transection had a marked reduction in distal femoral metaphysis BMD and a deterioration in bone structure and mechanical strength. When used to treat postmenopausal osteoporosis, romosozumab, a human monoclonal anti-sclerostin antibody, was more effective to increase bone mineral density (BMD) and to reduce fracture than any other anti-resorptive or bone-anabolic agent, and this effect was also evident for the appendicular skeleton, which is the site in individuals with chronic SCI of greatest bone loss and most frequent fracture. Because of the absence of clinical options available for the treatment of osteoporosis in individuals with chronic paralysis, the investigators have proposed to test an antagonist of sclerostin, which is a potent bone anabolic agent with proven efficacy in treating women with postmenopausal osteoporosis, to improve bone mass and reduce fragility fractures. Thirty-nine male and female subjects with chronic, motor-complete SCI (>3 post injury, American Spinal Injury Association Impairment Scale A & B) between the ages of 18 and 50 years old who have aBMD at the distal femur at the distal femur ?0.7 g/cm2 but ?1.0 g/cm2 will be recruited for participation in a randomized, double-blind, placebo-controlled, parallel group clinical trial. The outcome measures of the proposed study are bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and dual energy x-ray absorptiometry (DXA), and biochemical markers of bone resorption and formation. Specific Aim 1: To restore ?5% of baseline integral volumetric BMD (vBMD) at the distal femur measured by peripheral quantitative computed tomography (pQCT) with 12 months of romosozumab therapy (primary specific aim). Specific Aim 2: To maintain, or to further increase, the gain in the distal femur vBMD at 24 months post the baseline measurement with dual drug therapy (12 months romosozumab followed by 12 months of denosumab) (primary specific aim). Specific Aim 3: To demonstrate that the magnitude of change in biomarkers of bone formation at 1 month of romosozumab therapy are associated with the greatest change in distal femur vBMD at 12 and 24 months (secondary specific aim). Exploratory Aims: Additional variables by pQCT for changes in the proximal tibia vBMD, distal femur and proximal tibia trabecular BMD (tBMD), cortical BMD of the tibia (38% of the tibial length), microarchitecture at the distal tibia, and changes in areal BMD at the distal femur, proximal tibia, and total hip by DXA will be obtained. Additional time points for biomarkers for bone resorption & formation will be obtained and related to changes in BMD. If successful, this approach will change standard of care for persons with chronic SCI and increase the ability to perform upright rehabilitation activities.